Date of Degree

9-2020

Document Type

Dissertation

Degree Name

Ph.D.

Program

Psychology

Advisor

Mariann Weierich

Committee Members

Jin Fan

Jack Grinband

Deborah Walder

Subject Categories

Behavioral Neurobiology | Biological Psychology | Clinical Psychology | Developmental Neuroscience | Psychiatric and Mental Health

Keywords

functional connectome, functional maturity, vulnerable phenotype, resilient phenotype, trauma exposure, fMRI

Abstract

Background: Exposure to traumatic stress and adversity during the formative years of development can have adverse effects on mental health, neuroendocrine stress system function, and the brain, that persist into adulthood. One candidate mechanism that might confer vulnerability to enduring adverse outcomes of early life trauma is disruption of normal brain maturation. As the brain matures, functional interactions among brain regions change until the functional brain architecture (i.e., the functional connectome) reaches a mature state in adulthood. Given that different neural circuits have distinct developmental trajectories and sensitive periods, traumatic stress at a given point in development might have distinct effects on different neural circuits and the brain as a whole. Whereas normative brain development has been extensively studied, little is known about the effects of traumatic stress on the development of the human functional connectome as a whole and of distinct neural networks specifically.

Aims and Hypotheses: Our first aim was to test the relationship between trauma exposure during development and atypical maturity of the functional connectome as a whole and of three network clusters separately in emerging adulthood. We hypothesized that trauma exposure would be associated with more age-atypical global functional maturity, greater functional maturity of the affective networks, lower functional maturity of the cognitive networks, and age-appropriate functional maturity of the sensory-motor networks. Our second aim was to determine the relative contributions of atypical global and network-specific functional maturity to adverse psychological and physiological outcomes of trauma exposure in emerging adulthood. We hypothesized that age-atypical global and network-specific functional maturity would be associated with specific trauma outcomes and would moderate the relationship between trauma exposure and trauma outcomes. Our third aim was to test the impact of trauma characteristics, including trauma timing, trauma type, and number of traumatic events, on the global and network-specific maturity of the functional connectome and trauma outcomes in emerging adulthood. We hypothesized that age-atypical global and network-specific functional maturity would moderate the relationship between specific trauma characteristics and trauma outcomes.

Method: 29 trauma-exposed (TE) women and 19 no-trauma (NTE) controls (ages 18-29) completed a resting-state functional magnetic resonance imaging (fMRI) scan and a structured clinical interview to assess trauma exposure and trauma-related symptoms. In addition, we measured sympathetic nervous system (SNS) activity and hypothalamic-pituitary-adrenal (HPA) axis activity, indexed by salivary alpha-amylase and cortisol, respectively, at baseline and in response to a trauma reminder. We used resting-state fMRI data from 79 healthy no-trauma controls ages 6-45 from the Nathan Kline Institute-Rockland Sample to build four normative models of functional connectome development using support vector regression: one global and three network-specific (cognitive, affective, and sensory-motor networks). We then used the four global and network-specific normative models to predict the age of each TE and NTE participant based on their whole-brain or network-specific functional connectivity. We tested trauma-related differences in global and network-specific maturity, indexed by signed and absolute differences between actual and predicted ages in TE and NTE women. We also tested associations between functional brain maturity and adverse trauma outcomes, including perceived stress, number of current psychiatric diagnoses, trauma-related symptoms, and stress system function. In addition, we tested associations between trauma characteristics, including trauma timing, trauma type, and number of traumatic events, and functional brain maturity. Finally, we tested functional brain maturity as a moderator of the relationship between trauma exposure and adverse trauma outcomes in emerging adulthood.

Results: TE women and NTE controls showed similar functional maturity of the brain as a whole and of the cognitive, affective, and sensory-motor networks separately. However, number of traumatic events was associated with more age-atypical global brain maturity, whereas history of sexual trauma was associated with more age-atypical affective network maturity in emerging adulthood. More age-atypical global brain maturity was in turn associated with a greater number of psychiatric diagnoses in emerging adulthood and moderated the relationship between number of psychiatric diagnoses and number of traumatic events. In addition, age-atypical global brain maturity moderated the relationship between age at the earliest trauma and number of psychiatric diagnoses, as well as basal SNS and HPA blunting. Finally, our preliminary follow-up analyses showed that lower affective network maturity in emerging adulthood was associated with adverse clinical outcomes, such as a greater number of current and lifetime psychiatric diagnoses, and blunted basal SNS activity in trauma-exposed women, especially those with a history of multiple traumatic events and sexual trauma during development.

Conclusions: Our results suggest that traumatic stress during development might disrupt brain maturation and result in age-atypical functional brain maturity in emerging adulthood. However, the effects of trauma on neurodevelopment and mental health outcomes depend on specific trauma characteristics, such as trauma timing, trauma type, and number of traumatic events. In addition, vulnerability to adverse clinical and physiological outcomes in trauma-exposed people seems to be related to two distinct processes: 1) a global shift towards accelerated maturation, which was associated with elevated HPA reactivity to trauma reminders, and 2) a delay in maturation of the affective circuits, which was associated with blunted basal SNS activity in emerging adulthood. Further, trauma-related factors, such as trauma timing, trauma type, and number of traumatic events, interact with global and affective network maturity to yield distinct clinical and physiological outcomes in emerging adulthood. Specifically, whereas greater global maturity and lower affective-network maturity might indicate a vulnerable phenotype, lower global maturity and greater affective-network maturity might indicate a resilient phenotype, particularly in TE women with a history of sexual trauma and multiple traumatic events early in life.

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